Assessing the performance of Coenzyme Q10 loaded DQAsomes to treat Leigh syndrome caused by NDUFS4 knockout

Abstract

Homozygous mutations in the NDUFS4 gene result in one of the many autosomal recessive forms of Leigh syndrome (LS), which impairs mitochondrial complex I function. In time, this disorder results in mental and motor impairment, often resulting in death. LS has no cure, and treatment focuses on symptom management. The delivery of CoQ10 can be improved in treating LS when caused by mutations in the NDUFS4 gene. Its poor solubility and bioavailability limit its clinical use as a preventative for oxidative damage and mitochondrial function. In this study, we developed CoQ10-loaded DQAsomes, utilizing dequalinium chloride -a bolalipid known for its antimicrobial properties to improve mitochondrial delivery of CoQ10. These DQAsomes were evaluated in an NDUFS4 knockout mouse model. Mitochondria from lung tissue of 32 knock-out mice and matched controls were isolated and CoQ10 uptake was quantified using fluorescence microscopy. Mitochondrial proteins were measured through ELISA, Western Blot, and PCR, and histopathological examination was per formed to support the findings. The DQAsomes were measured to be approximately 151.3 nm with a poly dispersity index (PDI) of 0.181, and mitochondrial uptake was found to be around 91.2 %. The apoptosis score measured following pure-CoQ10 administration was found to be 5.5 times higher compared to DQAsomes, while the inflammation score measured following DQAsomes administration was found to be 6.2 times lower than pure-CoQ10. Overall, these findings suggest promising therapeutic potential for DQAsomes in LS management, emphasizing their role in targeted mitochondrial CoQ10 delivery and potential clinical application.